Search

Aims To investigate the effect of Lactobacillus rhamnosus on viral replication and cellular response to human rhinovirus (HRV) infection, including the secretion of antiviral and inflammatory mediators from well-differentiated nasal epithelial cells (WD-NECs). Methods and results The WD-NECs from healthy adult donors (N  = 6) were cultured in vitro , exposed to different strains of L. rhamnosus (D3189, D3160, or LB21), and infected with HRV (RV-A16) after 24 h. Survival and adherence capacity of L. rhamnosus in a NEC environment were confirmed using CFSE-labelled isolates, immunofluorescent staining, and confocal microscopy. Shed virus and viral replication were quantified using TCID50 assays and RT-qPCR, respectively. Cytotoxicity was measured by lactate dehydrogenase (LDH) activity. Pro-inflammatory mediators were measured by multiplex immunoassay, and interferon (IFN)-λ1/3 was measured using a standard ELISA kit. Lactobacillus rhamnosus was able to adhere to and colonize WD-NECs prior to the RV-A16 infection. Lactobacillus rhamnosus did not affect shed RV-A16, viral replication, RV-A16-induced IFN-λ1/3 production, or LDH release. Pre-exposure to L. rhamnosus , particularly D3189, reduced the secretion of RV-A16-induced pro-inflammatory mediators by WD-NECs. Conclusions These findings demonstrate that L. rhamnosus differentially modulates RV-A16-induced innate inflammatory immune responses in primary NECs from healthy adults. [ABSTRACT FROM AUTHOR]

Background Rhinology procedures represent a wide and diverse category of procedures, which, on the surface, can appear very similar. Thus, it is difficult to navigate postoperative presentations in the general practice setting. Objective This article provides a comprehensive guide to managing acute presentations that might arise in primary care settings following common rhinology surgeries. It outlines common complications, their potential aetiology and first-aid measures that might be employed to temporise patients prior to escalation. It also provides a guide as to potential red flag symptomatology, and when and how to escalate specific presentations. Discussion Most acute postoperative complications can be effectively managed, or at the very least temporised, in the community setting. When in doubt, discuss with your local otolaryngologist or nearest centre with otolaryngology cover. [ABSTRACT FROM AUTHOR]

Background: Topical steroids are first‐line treatment for chronic rhinosinusitis (CRS), but fail to provide adequate symptom control for all patients. Designed for medical treatment failures, LYR‐210 is an implantable matrix that locally elutes mometasone furoate to inflamed sinonasal tissue for up to 24 weeks in CRS patients. In an open‐label phase 1 study, LYR‐210 demonstrated clinically relevant improvement in the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Safety and efficacy of LYR‐210 in CRS were evaluated in the LANTERN Phase 2 study. Methods: Sixty‐seven surgically naive adult CRS patients who were inadequately controlled by previous medical management and seeking an alternative treatment enrolled in a multicenter, blinded, controlled, dose‐ranging study. Patients had moderate‐to‐severe disease based on SNOT‐22 and composite 7‐day average scores of the 4 cardinal CRS symptoms (4CS), with diagnosis confirmed by nasal endoscopy and magnetic resonance imaging. Patients were randomized (1:1:1) to saline irrigation–only control or bilateral in‐office administration of LYR‐210 (2500 μg) or LYR‐210 (7500 μg). Safety and efficacy were evaluated over 24 weeks. Results: Both LYR‐210 doses were safe and well‐tolerated over the 24‐week treatment period. LYR‐210 demonstrated rapid and durable dose‐dependent symptom improvement based on 4CS and SNOT‐22, with LYR‐210 (7500 μg) achieving statistical significance as early as 8 weeks and out to 24 weeks compared with control. LYR‐210 (7500 μg) reduced rescue treatment use and radiographic ethmoid opacification at week 24. Conclusions: LYR‐210 is the first implantable sinonasal treatment to achieve up to 24 weeks of benefit from a single administration in surgically naive CRS patients with and without nasal polyps. [ABSTRACT FROM AUTHOR]

Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg) was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779). In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg) was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003). Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.